Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

He, Xiaojing; Jingyuan, Xiao; Zhao, Li; Ye, Mengling; Jia, Lin; Liu, Zhen; Liang, Yubing; Dai, Huijun; Ren, Jianmin; Lin, Fei

doi:10.1007/s10753-022-01762-6

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…Immunohistochemical staining. Immunohistochemistry was performed as previously described (26). Briefly, the synovial tissues were cut into 7 µm thick sections.…”

Section: Methodsmentioning

confidence: 99%

MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain

Chen

et al. 2023

Mol Med Rep

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Pain is the hallmark symptom of osteoarthritis (OA), and current analgesic treatments may be insufficient or have potentially adverse effects. The inhibition of Monoacylglycerol lipase (MAGL) produces anti-inflammatory and anti-nociceptive effects. However, the potential mechanism of MAGL in OA pain remains unclear. In the present study, the synovial tissues were removed from OA patients and mice. Immunohistochemical staining and western blotting were used to detect the expression of MAGL. M1 and M2 polarization markers were detected by flow cytometry and western blotting, and the mitophagy levels were detected by the immunofluorescence staining of mitochondrial autophagosomes with lysosomes and western blotting. The OA mice were intraperitoneally injected with MJN110 to inhibit MAGL once a day for a week. Mechanical and thermal pain thresholds were detected by electronic Von Frey and hot plate methods on days 0, 3, 7, 10, 14, 17, 21, and 28. The accumulation of MAGL in the synovial tissues of OA patients and mice promoted the polarization of macrophages towards an M1 phenotype. Pharmacological inhibition and siRNA knockdown of MAGL promoted polarization of M1 macrophages towards an M2 phenotype. MAGL inhibition increased the mechanical and thermal pain thresholds of OA mice and enhanced the mitophagy levels of M1 macrophages. In conclusion, in the present study, it was shown that MAGL regulated synovial macrophage polarization by inhibiting mitophagy in OA.

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“…Immunohistochemical staining. Immunohistochemistry was performed as previously described (26). Briefly, the synovial tissues were cut into 7 µm thick sections.…”

Section: Methodsmentioning

confidence: 99%

MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain

Chen

et al. 2023

Mol Med Rep

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“…This leads to a decrease in the secretion of inflammatory factors and an inhibition of M0 polarization towards M1. 42 In M1 macrophages treated with PI3K inhibitors, protein levels of p-AKT and the AKT downstream factor p-mTOR were significantly reduced, the PI3K/AKT pathway was inhibited, CD206 and iNOS levels in M1 were enhanced, and pro-inflammatory factors IL-12, TNF-α, and IL-6 were increased, promoting M1 polarization and accelerating inflammatory factor expression. 12 , 43 Phosphorylation of AKT activates degradation of the NF-κB inhibitor kinase IKB, NF-κB is then allowed to leave the cytoplasm and move into the nucleus, where it begins to express genes that it targets to support cell survival, thereby promoting M1 by inhibiting PI3K signaling and activating NF-κB signaling.…”

Section: Signaling Pathways and Factors Related To Macrophage Polariz...mentioning

confidence: 96%

Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis

Hu,

Shang,

Yang

et al. 2023

JIR

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Bone homeostasis is a dynamic equilibrium state of bone formation and absorption, ensuring skeletal development and repair. Bone immunity encompasses all aspects of the intersection between the skeletal and immune systems, including various signaling pathways, cytokines, and the crosstalk between immune cells and bone cells under both homeostatic and pathological conditions. Therefore, as key cell types in bone immunity, macrophages can polarize into classical pro-inflammatory M1 macrophages and alternative anti-inflammatory M2 macrophages under the influence of the body environment, participating in the regulation of bone metabolism and playing various roles in bone homeostasis. M1 macrophages can not only act as precursors of osteoclasts (OCs), differentiate into mature OCs, but also secrete pro-inflammatory cytokines to promote bone resorption; while M2 macrophages secrete osteogenic factors, stimulating the differentiation and mineralization of osteoblast precursors and mesenchymal stem cells (MSCs), and subsequently increase bone formation. Once the polarization of macrophages is imbalanced, the resulting immune dysregulation will cause inflammatory stimulation, and release a large amount of inflammatory factors affecting bone metabolism, leading to pathological conditions such as osteoporosis (OP), rheumatoid arthritis (RA), and steroid-induced femoral head necrosis (SANFH). In this review, we introduce the signaling pathways and related factors of macrophage polarization, as well as their relationships with immune factors, OB, OC, and MSC. We also discuss the roles of macrophage polarization and bone immunity in various diseases of bone homeostasis imbalance, as well as the factors regulating them, which may help to develop new methods for treating bone metabolic disorders.

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“…Such regulations are potentially negated by Src Kinase Associated Phosphoprotein 2 (SKAP2), implying a role in inflammation-driven oncogenesis [38]. Within immune cell modulation, SHP2 and SHP1 respectively influence M1 phenotype activation in TAM and T-cell inactivation [39,40].…”

Section: Siglecs and Ligand-mediated Immune Evasion Mechanisms In Onc...mentioning

confidence: 99%

The Potential of Siglecs and Sialic Acids as Biomarkers and Therapeutic Targets in Tumor Immunotherapy

Feng,

Han

et al. 2024

Cancers

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The dysregulation of sialic acid is closely associated with oncogenesis and tumor progression. Most tumor cells exhibit sialic acid upregulation. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are receptors that recognize sialic acid and are expressed in various immune cells. The activity of Siglecs in the tumor microenvironment promotes immune escape, mirroring the mechanisms of the well-characterized PD-1/PD-L1 pathway in cancer. Cancer cells utilize sialic acid-linked glycans to evade immune surveillance. As Siglecs exhibit similar mechanisms as the established immune checkpoint inhibitors (ICIs), they are potential therapeutic targets for different forms of cancer, especially ICI-resistant malignancies. Additionally, the upregulation of sialic acid serves as a potential tumor biomarker. This review examines the feasibility of using sialic acid and Siglecs for early malignant tumor detection and discusses the potential of targeting Siglec–sialic acid interaction as a novel cancer therapeutic strategy.

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Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

Cited by 10 publications

References 40 publications

MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain

MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain

Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis

The Potential of Siglecs and Sialic Acids as Biomarkers and Therapeutic Targets in Tumor Immunotherapy

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